OAS2 (2'-5'-oligoadenylate synthetase 2) is an interferon-induced, dsRNA-activated antiviral enzyme critical for innate immunity 1. Upon detecting double-stranded RNA, OAS2 synthesizes 2'-5'-oligoadenylates (2-5A) that activate ribonuclease L (RNASEL), leading to degradation of viral and cellular RNA and inhibition of protein synthesis 12. OAS2 comprises two OAS domains, with the catalytically deficient domain acting as a molecular ruler to discriminate RNA length and prevent autoreactivity 3. Myristoylation-mediated localization to Golgi membranes is required for OAS2 activation and restriction of endomembrane-replicating viruses like coronaviruses 3. Beyond RNASEL-dependent pathways, OAS2 mediates alternative antiviral mechanisms and regulates apoptosis, cell growth, and differentiation 4. OAS2 dysfunction has clinical significance: loss-of-function mutations associate with autoimmune disease 3, recessive OAS2 deficiencies underlie multisystem inflammatory syndrome in children following COVID-19 by unleashing excessive MAVS-mediated cytokine production 5, and genetic variants influence COVID-19 severity 6. OAS2 expression increases in psoriatic skin and contributes to keratinocyte proliferation via JAK1-STAT1 signaling 7.